Assistant Professor, University of Texas MD Anderson Cancer Center
Reprogramming Antigen Presentation in Pancreatic Cancer Using Immunostimulatory Antibody-Drug Conjugates
Overview
Aim: Treatment/Therapy
The immune system has two domains: innate and adaptive immunity. Evolutionarily older, innate immune cells called phagocytes continuously search the body for infected cells and “eat” them in a process called phagocytosis. In turn, the innate immune system trains the adaptive one to provide a more targeted response that drives lasting immunity. While many cancer immunotherapies focus on activating the adaptive immune system, most patients with pancreatic cancer still do not respond.
One promising alternative is to engage the innate immune system. However, most cancer cells display “don’t eat me” signals, such as a protein called CD47, that stops phagocytes from engulfing them. To overcome this, we developed a new therapy called CD47-LLO. This therapy targets CD47 and prompts phagocytes to eat pancreatic cancer cells. Once the cancer cells are engulfed, a protein called Listeriolysin O (LLO) is activated inside the phagocytes. LLO helps preserve cancer proteins that would otherwise be broken down, allowing the phagocyte to display them on its surface and present them to adaptive immune cells. We hypothesize this process helps phagocytes more effectively “teach” the adaptive immune system to recognize and attack pancreatic cancer. This study will test how CD47- LLO enhances communication between innate and adaptive immune cells and whether it can boost the effectiveness of other immunotherapies. If successful, this study could lay the foundation for a clinical trial of CD47-LLO in patients with pancreatic cancer.
